BMA Concise Guide to Medicine & Drugs

BRAIN AND NERVOUS SYSTEM

The human brain contains more than 100 billion nerve cells (neurons). These nerve cells receive electrochemical impulses from everywhere in the body. They interpret these impulses and send responsive signals back to various glands and muscles. The brain functions continuously as a switchboard for the human communications system. At the same time, it serves as the seat of emotions and mood, of memory, personality, and thought. Extending from the brain is an additional, large rod-shaped cluster of nerve cells that forms the spinal cord. Together, these two elements comprise the central nervous system.

Radiating from the central nervous system is the peripheral nervous system, which has three parts. One branches off the spinal cord and extends to skin and muscles throughout the body. Another, in the head, links the brain to the eyes, ears, nose, and taste buds. The third is a semi-independent network called the autonomic, or involuntary, nervous system. This is the part of the nervous system that controls unconscious body functions such as breathing, digestion, and glandular activity.

Signals traverse the nervous system by electrical and chemical means. Electrical impulses carry signals from one end of a neuron to the other. To cross the gap between neurons, chemical neurotransmitters are released from one cell to bind on to the receptor sites of nearby cells. Excitatory transmitters stimulate action; inhibitory transmitters reduce it.

WHAT CAN GO WRONG

Disorders of the brain and nervous system may manifest as illnesses that show themselves as physical impairments, such as epilepsy or strokes, or mental and emotional impairments (for example, schizophrenia or depression).

Illnesses causing physical impairments can result from different types of disorder of the brain and nervous system. Death of nerve cells resulting from poor circulation can result in paralysis, while electrical disturbances of certain nerve cells cause the seizures of epilepsy. Temporary changes in blood circulation within and around the brain are associated with migraine. Parkinson’s disease is caused by a lack of dopamine, a neurotransmitter that is produced by specialized brain cells.

The causes of disorders that trigger mental and emotional impairment are not known, but these illnesses are thought to result from the defective functioning of nerve cells and neurotransmitters.

WHY DRUGS ARE USED

By and large, the drugs described in this section do not eliminate nervous system disorders. Their function is to correct or modify the communication of the signals that traverse the nervous system. By doing so they can relieve symptoms or restore normal functioning and behaviour. In some cases, such as anxiety and insomnia, drugs are used to lower the level of activity in the brain. In other disorders (depression, for example) drugs are given to encourage the opposite effect, increasing the level of activity.

Drugs that act on the nervous system are also used for conditions that outwardly have nothing to do with nervous system disorders. Vomiting, for example, may be treated with drugs that directly affect the vomiting centre in the brain or block stimulatory nerve signals to the vomiting centre.

AUTONOMIC NERVOUS SYSTEM

The autonomic, or involuntary, nervous system governs the actions of the muscles of the organs and glands. Such vital functions as heart beat and digestion continue without conscious direction, whether we are awake or asleep.

The autonomic nervous system is divided into two parts, the effects of one generally balancing those of the other. The sympathetic nervous system has an excitatory effect. For example, it widens the airways to the lungs, increases the heart rate, and increases the flow of blood to the arms and legs. The parasympathetic system, by contrast, has an opposing effect. It slows the heart rate, narrows the large airways, and redirects blood from the limbs to the gut.

Although the functional pace of most organs results from the interplay between the two systems, the muscles in the blood vessel walls respond only to the signals of the sympathetic nervous system. Whether a vessel is dilated or constricted is determined by the relative stimulation of two sets of receptor sites: alpha sites and beta sites.

Blood vessels in the skin These are constricted by stimulation of alpha receptors by the sympathetic; the parasympathetic has no effect on them.

The heart The rate and strength of the heart are increased by the sympathetic and reduced by the parasympathetic.

The pupils These are dilated by the sympathetic and constricted by the parasympathetic.

The airways The bronchial muscles are relaxed and widened by the sympathetic and contracted and narrowed by the parasympathetic.

Intestines The activity of the intestinal wall muscles is reduced by the sympathetic and increased by the parasympathetic.

NEUROTRANSMITTERS

The parasympathetic nervous system depends on the neurotransmitter acetylcholine to transmit signals from one cell to another. The sympathetic nervous system relies on adrenaline and noradrenaline, substances that act as both hormones and neurotransmitters.

DRUGS THAT ACT ON THE SYMPATHETIC NERVOUS SYSTEM

The drugs that stimulate the sympathetic nervous system are called adrenergics (or sympathomimetics). They either promote the release of epinephrine (adrenaline) and norepinephrine (noradrenaline) or mimic their effects. Drugs that interfere with the action of the sympathetic nervous system are called sympatholytics. Alpha blockers act on alpha receptors; beta blockers act on beta receptors (see also Beta blockers).

DRUGS THAT ACT ON THE PARASYMPATHETIC NERVOUS SYSTEM

Drugs that stimulate the parasympathetic nervous system are called cholinergics (or parasympathomimetics); drugs that oppose its action are called anticholinergics. Many prescribed drugs have anticholinergic properties.

MAJOR DRUG GROUPS

· Analgesics

· Sleeping drugs

· Anti-anxiety drugs

· Antidepressant drugs

· Antipsychotic drugs

· Antimanic drugs

· Anticonvulsant drugs

· Drugs for parkinsonism

· Drugs for dementia

· Nervous system stimulants

· Drugs used for migraine

· Anti-emetics

Analgesics

Analgesics (painkillers) are drugs that relieve pain. Since pain is not a disease but a symptom, long-term relief depends on treatment of the underlying cause. For example, the pain of toothache can be relieved by drugs but can be cured only by appropriate dental treatment. If the underlying disorder, such as some rheumatic conditions, is irreversible, long-term analgesic treatment may be necessary.

Damage to body tissues as a result of disease or injury is detected by nerve endings that transmit signals to the brain. Interpretation of these sensations can be affected by a person’s psychological state, so that pain is worsened by anxiety and fear, for example. Often a reassuring explanation of the cause of discomfort can make pain easier to bear and may even relieve it altogether. Anti-anxiety drugs are helpful when pain is accompanied by anxiety, and some of these drugs are also used to reduce painful muscle spasms. Some antidepressants act to block the transmission of impulses signalling pain and are particularly useful for nerve pains (neuralgia), which do not always respond to analgesics.

TYPES OF ANALGESICS

Analgesics are divided into the opioids (with similar properties to drugs derived from opium, such as morphine) and non-opioids. Non-opioids include all the other analgesics, including paracetamol, nefopam, and also non-steroidal anti-inflammatory drugs (NSAIDs), the most well known of which is aspirin. The non-opioids are all less powerful as painkillers than the opioids. Local anaesthetics are also used to relieve pain.

Opioid drugs and paracetamol act directly on the brain and spinal cord to alter the perception of pain. Opioids act like the endorphins, hormones naturally produced in the brain that stop the cell-to-cell transmission of pain sensation. NSAIDs block the formation of pain-modulating substances (e.g. prostaglandins) at nerve endings at the site of pain.

When pain is treated under medical supervision, it is common to start with paracetamol or an NSAID; if neither provides adequate pain relief, they may be combined. A mild opioid such as codeine may also be used. If the less powerful drugs are ineffective, a strong opioid such as morphine may be given. As there is now a wide variety of oral analgesic formulations, injections are seldom necessary to control even the most severe pain.

When using an over-the-counter preparation (for example, taking paracetamol for a headache) you should seek medical advice if pain persists for longer than 48 hours, recurs, or is worse or different from previous pain.

NON-OPIOID ANALGESICS

Paracetamol This analgesic is believed to act by reducing the production of chemicals called prostaglandins in the brain. However, paracetamol does not affect prostaglandin production in the rest of the body, so it does not reduce inflammation, although it can reduce fever. Paracetamol can be used for everyday aches and pains, such as headaches, toothache, and joint pains.

As well as being the most widely used analgesic, it is one of the safest when taken correctly. It does not usually irritate the stomach and allergic reactions are rare. However, an overdose can cause severe and possibly fatal liver or kidney damage. Its toxic potential may be increased in heavy drinkers.

Non-steroidal anti-inflammatory drugs (NSAIDs): aspirin Used for many years to relieve pain and reduce fever, aspirin also reduces inflammation by blocking the production of prostaglandins, which contribute to the swelling and pain in inflamed tissue. Aspirin is useful for headaches, toothache, mild rheumatic pain, sore throat, and discomfort caused by feverish illnesses. Given regularly, it can also relieve the pain and inflammation of chronic rheumatoid arthritis (see Antirheumatic drugs).

Aspirin is found in combination with other substances in a variety of medicines (see Cold cures). It is also used in the treatment of some blood disorders, since aspirin helps to prevent abnormal clotting of blood by preventing platelets from sticking together (see Drugs that affect blood clotting).

Aspirin in the form of soluble tablets, dissolved in water before being taken, is absorbed into the bloodstream more quickly, thereby relieving pain faster than tablets. Soluble aspirin is not less irritating to the stomach lining, however.

Aspirin is available in many forms, all of which have a similar effect, but because the amount of aspirin in a tablet of each type varies, it is important to read the packet for the correct dosage. It is not recommended for children aged under 16 years because its use has been linked to Reye’s syndrome, a rare but potentially fatal liver and brain disorder.

Other non-steroidal anti-inflammatory drugs (NSAIDs) These drugs can relieve both pain and inflammation. NSAIDs are related to aspirin and also work by blocking the production of prostaglandins. They are most commonly used to treat muscle and joint pain and may also be prescribed for other types of pain including period pain. For further information, see non-steroidal anti-inflammatory drugs.

COMBINED ANALGESICS

Mild opioids, such as codeine, are often found in combination preparations with non-opioids, such as paracetamol. The prefix “co-” is used to denote a drug combination. Although both opioids and paracetamol act centrally, these mixtures have the advantage of combining different mechanisms of action. Another advantage of combining analgesics is that the reductions in dose of the components may reduce the side effects of the preparation. Combinations can be helpful in reducing the number of tablets taken during long-term treatment.

OPIOID ANALGESICS

These drugs are related to opium, an extract of poppy seeds. They act directly on several sites in the central nervous system to block the transmission of pain signals. Because they act directly on the parts of the brain where pain is perceived, opioids are the strongest analgesics and are therefore used to treat the pain arising from surgery, serious injury, and cancer. These drugs are particularly valuable for relieving severe pain during terminal illnesses. In addition, their ability to produce a state of relaxation and euphoria is often of help in relieving the stress that accompanies severe pain.

Morphine is the best-known opioid analgesic. Others include diamorphine (heroin) and pethidine. The use of these powerful opioids is strictly controlled because the euphoria produced can lead to abuse and addiction. When these opioids are given under medical supervision to treat severe pain, the risk of addiction is negligible.

Opioid analgesics may prevent clear thought and cloud consciousness. Otherpossible adverse effects include nausea, vomiting, constipation, drowsiness, and depressed breathing. When they are taken in overdose, these drugs may induce a deep coma and lead to fatal breathing difficulties.

In addition to the powerful opioids, there are some less powerful drugs in this group that are used to relieve mild to moderate pain. They include codeine and tramadol. The opioids’ normally unwanted side effects of depressing respiration and causing constipation make them useful as cough suppressants and as antidiarrhoeal drugs.

LOCAL ANAESTHETICS

These drugs are used to prevent pain, usually in minor surgical procedures (for example, dental treatment and stitching cuts). They can also be injected into the space around the spinal cord to numb the lower half of the body. This is called spinal or epidural anaesthesia and can be used for some major operations in people who are not fit for a general anaesthetic. Epidural anaesthesia is also used during childbirth.

Local anaesthetics block the passage of nerve impulses at the site of administration, deadening all feeling conveyed by the nerves with which they come into contact. They do not interfere with consciousness, however. Local anaesthetics are usually given by injection but can also be applied to the skin, mouth, and other areas lined with mucous membrane (such as the vagina), or the eye to relieve pain. Some local anaesthetics are formulated for injection together with epinephrine (adrenaline). Epinephrine constricts the blood vessels and prevents the local anaesthetic from being absorbed into the bloodstream. This action keeps the anaesthetic at the site, thus prolonging its effect.

Local anaesthetic creams are often used to numb the skin before injections in children and those people with a fear of needles.

COMMON DRUGS

Opioids Buprenorpine, Co-codamol, Codeine, Co-dydramol, Diamorphine (heroin), Dihydrocodeine, Dipipanone, Fentanyl, Meptazinol, MethadoneMorphine, Oxycodone, Pethidine, Tramadol

NSAIDs AspirinDiclofenac, Etodolac, Fenbufen, Fenoprofen, Ibuprofen, Indometacin, Ketoprofen, Mefenamic acid, Meloxicam, NaproxenPiroxicam

Other non-opioids Nefopam, Paracetamol

Local anaesthetics Bupivacaine, Lidocaine

Sleeping drugs

Difficulty in getting to sleep or staying asleep (insomnia) has many causes. Most people have sleepless nights from time to time, usually due to a temporary worry or discomfort from a minor illness. Persistent sleeplessness can be caused by psychological problems including anxiety or depression, or the pain and discomfort of a physical disorder.

WHY THEY ARE USED

For occasional sleeplessness, simple, common remedies to promote relaxation, such as taking a warm bath or a hot milk drink before bedtime, are usually the best treatment. Sleeping drugs (also known as hypnotics) are normally prescribed only when these self-help remedies have failed, and when lack of sleep is beginning to affect general health. They are used to re-establish the habit of sleeping, and should be used in the smallest dose and for the shortest possible time (not more than three weeks). It is best not to use sleeping tablets every night (see Risks and special precautions). Do not use alcohol to get to sleep as it can cause disturbed sleep and insomnia. Long-term treatment of sleeplessness depends on resolving the underlying cause.

TYPES OF SLEEPING DRUGS

Benzodiazepines are the most commonly used class of sleeping drug because they have comparatively few adverse effects and are relatively safe in overdose. They are also used to treat anxiety.

Barbiturates are now almost never used because of the risks of abuse, dependence, and toxicity in overdose. There is also a risk of prolonged sedation (“hangover”).

Chloral derivatives effectively promote sleep but are little used now. If prescribed, triclofos causes fewer gastrointestinal side effects than chloral hydrate.

Other non-benzodiazepine sleeping drugs Zopiclone, zaleplon, and zolpidem are non-benzodiazepine sleeping drugs that work in a similar way to benzodiazepines. They are not intended for long-term use, and withdrawal symptoms have been reported.

Antihistamines are widely used to treat allergic symptoms. Because they also cause drowsiness, they are sometimes used to promote sleep.

Antidepressant drugs may be used to promote sleep in depressed people as well as being effective in treating underlying depressive illness.

HOW THEY WORK

Most sleeping drugs promote sleep by depressing brain function. The drugs interfere with chemical activity in the brain and nervous system by reducing communication between nerve cells. This leads to reduced brain activity, allowing you to fall asleep more easily, but the nature of the sleep is affected by the drug. For more information, see the main class of sleeping drugs, the benzodiazepines.

HOW THEY AFFECT YOU

A sleeping drug rapidly produces drowsiness and slowed reactions. Some people find that the drug makes them appear to be drunk, their speech slurred, especially if they delay going to bed after taking their dose. Most people find they usually fall asleep within one hour of taking the drug.

Because the sleep induced by drugs is not the same as normal sleep, many people find that they do not feel as well rested by it as by a night of natural sleep. This is the result of suppressed brain activity. Sleeping drugs also suppress the sleep during which dreams occur; both dream sleep and non-dream sleep are essential for a good night’s sleep.

Some people experience a variety of hangover effects the following day. Some benzodiazepines may produce minor side effects, such as daytime drowsiness, dizziness, and unsteadiness, that can impair the ability to drive or operate machinery. Elderly people are likely to become confused and, for them, the selection of an appropriate drug is important.

RISKS AND SPECIAL PRECAUTIONS

Sleeping drugs become less effective after the first few nights and there may be a temptation to increase the dose. Apart from the antihistamines, most sleeping drugs can produce psychological and physical dependence when taken regularly for more than a few weeks, especially if they are taken in larger-than-normal doses.

When sleeping drugs are suddenly withdrawn, anxiety, seizures, and hallucinations sometimes occur. Nightmares and vivid dreams may be a problem because the time spent in dream sleep increases. Sleeplessness will recur and may lead to a temptation to use sleeping drugs again. Anyone who wishes to stop taking sleeping drugs, particularly after prolonged use, should seek his or her doctor’s advice to prevent these withdrawal symptoms from occurring.

COMMON DRUGS

Benzodiazepines Flurazepam, Loprazolam, Lormetazepam, NitrazepamTemazepam

Other non-benzodiazepine sleeping drugs Clomethiazole, Promethazine, Zaleplon, Zolpidem, Zopiclone

Anti-anxiety drugs

A certain amount of stress can be beneficial, providing a stimulus to action. But too much will often result in anxiety, which might be described as fear or apprehension not caused by real danger.

Clinically, anxiety arises when the balance of certain chemicals in the brain is disturbed. The fearful feelings increase brain activity, stimulating the sympathetic nervous system (see Autonomic nervous system) and often triggering physical symptoms, for example, breathlessness, shaking, palpitations, digestive distress, and headaches.

WHY THEY ARE USED

Anti-anxiety drugs (also known as anxiolytics or minor tranquillizers) are prescribed for short-term relief of severe anxiety and nervousness caused by psychological problems. However, these drugs cannot resolve the causes. Tackling the underlying problem through counselling and perhaps psychotherapy offers the best hope of a long-term solution. Anti-anxiety drugs are also used in hospitals to calm and relax people undergoing uncomfortable medical procedures.

There are two main classes of drug for relieving anxiety: benzodiazepines and beta blockers. Benzodiazepines, which are the most widely used, are given as regular treatment for short periods to promote relaxation. Most benzodiazepines have a strong sedative effect, helping to relieve the insomnia that accompanies anxiety (see also Sleeping drugs).

Beta blockers are mainly used to reduce physical symptoms of anxiety, such as shaking and palpitations. These drugs are commonly prescribed for people who feel excessively anxious in certain situations, such as interviews or public appearances.

Many antidepressants, including SSRIs, clomipramine, and venlafaxine, are proving useful in some anxiety disorders.

HOW THEY WORK

Benzodiazepines and related drugs depress activity in the part of the brain that controls emotion by promoting the action of the neurotransmitter gamma-aminobutyric acid (GABA), which binds to neurons, blocking transmission of electrical impulses and thereby reducing communication between brain cells. Benzodiazepines increase the inhibitory effect of GABA on brain cells, preventing the excessive brain activity that causes anxiety.

Buspirone is different from other anti-anxiety drugs; it binds mainly to serotonin (another neurotransmitter) receptors and does not cause drowsiness. Its effect is not felt for at least two weeks after treatment has begun.

Beta blockers block the action of a chemical transmitter called norepinephrine (noradrenaline) in the body, reducing the physical symptoms of anxiety. These symptoms are produced by an increase in the activity of the sympathetic nervous system. Sympathetic nerve endings release norepinephrine, which stimulates the heart, digestive system, and other organs. For more information, see beta blockers.

HOW THEY AFFECT YOU

Benzodiazepines and related drugs reduce feelings of restlessness and agitation, slow mental activity, and often produce drowsiness. They are said to reduce motivation and, if they are taken in large doses, may lead to apathy. They also have a relaxing effect on the muscles, and some benzodiazepines are used specifically for that purpose (see Muscle relaxants).

Minor adverse effects of these drugs include dizziness and forgetfulness. People who need to drive or operate potentially dangerous machinery should be aware that their reactions may be slowed. Because the brain soon becomes tolerant to and dependent on their effects, benzodiazepines are usually effective for only a few weeks at a time.

Beta blockers reduce the physical symptoms associated with anxiety, which may promote greater mental calmness. Because they do not cause drowsiness, they are safer for people who need to drive.

RISKS AND SPECIAL PRECAUTIONS

The benzodiazepines are safe for most people and less dangerous in overdose than other sedative drugs. The main risk is psychological and physical dependence, especially for regular users or with larger-than-average doses. For this reason, they are usually given for courses of two weeks or less. If they have been used for longer, they should be withdrawn gradually under medical supervision. If they are stopped suddenly, withdrawal symptoms, such as excessive anxiety, nightmares, and restlessness, may occur.

Benzodiazepines have been abused for their sedative effect, and are therefore prescribed with caution for people with a history of drug or alcohol abuse.

COMMON DRUGS

Benzodiazepines Alprazolam, Chlordiazepoxide, Diazepam/Lorazepam, Oxazepam

Beta blockers Atenolol, Bisoprolol, Oxprenolol, Propranolol

Other non-benzodiazepines Buspirone

Antidepressant drugs

Occasional moods of discouragement or sadness are normal and usually pass quickly. However, more severe depression that is accompanied by despair, lethargy, loss of sex drive, and often poor appetite may call for medical attention. Such depression can arise from life stresses such as the death of someone close, an illness, or sometimes from no apparent cause.

There are three main types of drug for depression: tricyclic antidepressants (TCAs), selective serotonin re-uptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs). Lithium, a metallic element, is used to treat manic depression (see Antimanic drugs). In some cases, it is used with an antidepressant for treating resistant depression. Several other antidepressants may be prescribed, including venlafaxine, mirtazepine, mianserin, and trazodone.

WHY THEY ARE USED

Minor depression does not usually require drug treatment; support and help in coming to terms with the cause is often all that is needed. Moderate or severe depression usually requires drug treatment, which is effective in most cases. Antidepressants may have to be taken for many months. Treatment should not be stopped too soon because symptoms are likely to reappear. When treatment is stopped, the dose should be reduced gradually over several weeks because withdrawal symptoms may occur if the drugs are stopped suddenly.

TYPES OF ANTIDEPRESSANT

Treatment usually begins with either a TCA or an SSRI.

TCAs Some TCAs (such as amitriptyline) cause drowsiness, which is useful for sleep problems in depression. TCAs also cause anticholinergic effects (see Drugs that act on the parasympathetic nervous system), including blurred vision, dry mouth, and urinary difficulties.

SSRIs These drugs generally have fewer side effects than TCAs. The main unwanted effects are nausea and vomiting. Anxiety, headache, and restlessness may also occur at the beginning of treatment.

MAOIs These are especially effective in people who are anxious as well as depressed, or who suffer from phobias.

Lithium Salts of this metallic element are used to treat manic depression (see Antimanic drugs). They are sometimes used with an antidepressant drug for resistant depression.

Other antidepressants These drugs include venlafaxine, duloxetine, flupentixol, mirtazepine, mianserin, and trazodone.

HOW THEY WORK

Normally, the brain cells release sufficient quantities of certain chemicals (known as neurotransmitters) in the brain to stimulate neighbouring cells. The neurotransmitters are constantly reabsorbed into the brain cells, where they are broken down by an enzyme called monoamine oxidase. Depression is thought to be caused by a reduction in the level of neurotransmitters in the brain. Antidepressants raise the level of these neurotransmitters.

TCAs and venlafaxine work by blocking the re-uptake of the neurotransmitters serotonin and norepinephrine (noradrenaline), thereby increasing the level of these neurotransmitters in the brain.

SSRIs act by blocking the re-uptake of only one neurotransmitter, serotonin.

MAOIs act by blocking the breakdown of neurotransmitters, mainly serotonin and norepinephrine (noradrenaline).

HOW THEY AFFECT YOU

The antidepressant effect of these drugs starts after 10 to 14 days of treatment, and it may be six to eight weeks before the full effect is seen. However, side effects may happen at once. Tolerance to these side effects usually occurs and treatment should be continued.

RISKS AND SPECIAL PRECAUTIONS

Overdose can be dangerous: tricyclic antidepressants can produce coma, seizures, and disturbed heart rhythm, which may be fatal; monoamine oxidase inhibitors can also cause muscle spasms and even death. Both are prescribed with caution for people with heart problems or epilepsy.

When MAOIs are taken with certain drugs or foods rich in tyramine (for example, cheese, meat, yeast extracts, and red wine), they can produce a dramatic rise in blood pressure, with headache or vomiting. People taking MAOIs are given a card that lists prohibited drugs and foods. Because of this adverse interaction, MAOIs are used much less frequently today, and SSRIs or tricyclics are prescribed in preference to them, although SSRIs are not generally prescribed to anyone under the age of 18, however.

COMMON DRUGS

Tricyclics Amitriptyline, Clomipramine, Dosulepin, Doxepin, Imipramine, Lofepramine, Nortriptyline, Trimipramine

SSRIs Citalopram/Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline

MAOIs Isocarboxazid, Moclobemide, Phenelzine, Tranylcypromine

Other drugs Duloxetine, Flupentixol, Mianserin, Mirtazepine Reboxetine, Trazodone, Tryptophan, Venlafaxine

Antipsychotic drugs

Psychosis is a term used to describe mental disorders that prevent the sufferer from think- ing clearly, recognizing reality, and acting rationally. These disorders include schizophrenia and bipolar disorder (manic depression). The precise causes of these disorders are unknown, although a number of factors, including stress, heredity, and brain injury, may be involved. Temporary psychosis can also arise as a result of alcohol withdrawal or the abuse of mind-altering drugs. Various drugs are used to treat psychotic disorders (see Common drugs), most have which have similar actions and effects. One exception is lithium, which is particularly useful for bipolar disorder (see Antimanic drugs).

WHY THEY ARE USED

A person with a psychotic illness may recover spontaneously, so a drug will not always be prescribed. Long-term treatment is started only when normal life is seriously disrupted. Antipsychotic drugs (also called major tranquillizers or neuroleptics) do not cure the disorder, but they do help to control symptoms.

By controlling the symptoms of psychosis, antipsychotic drugs make it possible for most sufferers to live in the community and only be admitted to hospital for acute episodes.

The drug given to a particular individual depends on the nature of his or her illness and the expected adverse effects of that drug. Drugs differ in the amount of sedation produced; the need for sedation also influences the choice of drug.

Antipsychotics may also be given to calm or sedate a highly agitated or aggressive person, whatever the cause. Some antipsychotic drugs also have a powerful action against nausea and vomiting, and are therefore sometimes used as premedication before a person has surgery.

HOW THEY WORK

It is thought that some forms of mental illness are caused by an increase in communication between brain cells due to overactivity of an excitatory chemical called dopamine. This may disturb normal thought processes and produce abnormal behaviour. Dopamine combines with receptors on the brain cells. Antipsychotic drugs reduce the transmission of nerve signals by binding to these receptors, thereby making the brain cells less sensitive to dopamine. Some newer antipsychotic drugs, such as clozapine, risperidone, and sertindole, also bind to receptors for the chemical serotonin.

HOW THEY AFFECT YOU

Because antipsychotics depress the action of dopamine, they can disturb its balance with another chemical in the brain, acetylcholine. If an imbalance occurs, extrapyramidal side effects (EPSE) may appear. These include restlessness, disorders of movement, and parkinsonism (see Drugs for parkinsonism).

In these circumstances, a change to a different type of antipsychotic may be necessary. If this is not possible, an anticholinergic drug may be prescribed.

Antipsychotics may block the action of noradrenaline, another neurotransmitter in the brain. This lowers the blood pressure, especially when you stand up, causing dizziness. It may also prevent ejaculation.

RISKS AND SPECIAL PRECAUTIONS

It is important to continue taking these drugs even if all symptoms have gone, because the symptoms are controlled only by taking the prescribed dose.

Because antipsychotic drugs can have permanent as well as temporary side effects, the minimum necessary dosage is used. This minimum dose is found by starting with a low dose and increasing it until the symptoms are controlled. Sudden withdrawal after more than a few weeks can cause nausea, sweating, headache, and restlessness. Therefore, the dose is reduced gradually when treatment needs to be stopped.

The most serious long-term risk of anti-psychotic treatment is a disorder known as tardive dyskinesia, which may develop after one to five years. This consists of repeated jerking movements of the mouth, tongue, and face, and sometimes of the hands and feet. The condition is less common with the newer antipsychotics (atypical antipsychotics) than the older drugs (typical antipsychotics).

HOW THEY ARE ADMINISTERED

Antipsychotics may be given by mouth as tablets, capsules, or syrup, or by injection. They can also be given in the form of an intramuscular depot injection, which releases the drug slowly over several weeks.

COMMON DRUGS

Typical antipsychotics Benperidol, Chlorpromazine, Flupentixol, Fluphenazine, Haloperidol, Levomepromazine, Pericyazine, Perphenazine, Pimozide, Pipotiazine, Prochlorperazine, Promazine, Trifluoperazine, Zuclopenthixol

Atypical antipsychotics Amisulpride, Aripiprazole, Clozapine, Olanzapine, Quetiapine, Risperidone, Sertindole, Zotepine

Antimanic drugs

Changes in mood are normal, but when a person’s mood swings become grossly exaggerated, with peaks of elation or mania alternating with troughs of depression, it becomes an illness known as bipolar disorder or manic depression. It is usually treated with salts of lithium, a drug that reduces the intensity of the mania, lifts the depression, and lessens the frequency of mood swings. Because it may take weeks or even months before the lithium starts to work, an antipsychotic may be prescribed with lithium at first to give immediate relief of symptoms.

Lithium can be toxic if blood levels of the drug rise too high. Regular checks on the blood concentration of lithium should therefore be carried out during treatment. Symptoms of lithium poisoning include blurred vision, tremor, vomiting, and diarrhoea.

COMMON DRUGS

Carbamazepine, Lithium

Anticonvulsant drugs

Electrical signals from nerve cells in the brain are normally finely coordinated to produce smooth movements of the arms and legs, but these signals can become irregular and chaotic, and trigger the disorderly muscular activity and mental changes that are characteristic of a seizure (also called a fit or convulsion). The most common cause of seizures is epilepsy, which occurs as a result of brain disease or injury. In epileptics, a seizure may be triggered by an outside stimulus such as a flashing light. Seizures can also result from the toxic effects of certain drugs and, in young children, by a high temperature.

Anticonvulsant drugs are used both to reduce the risk of an epileptic seizure and to stop one that is in progress.

WHY THEY ARE USED

Isolated seizures seldom require drug treatment, but anticonvulsant drugs are the usual treatment for controlling seizures caused by epilepsy. In most cases, they permit a person with epilepsy to lead a normal life.

Most people with epilepsy need to take anticonvulsants on a regular basis to prevent seizures. Usually a single drug is used, and treatment continues until there have been no attacks for at least two years.

If one drug is not effective, a different one will be tried. Occasionally, it is necessary to take a combination of drugs. Even when receiving treatment, a person can suffer seizures. Repeated seizures or status epilepticus can be halted by injection of diazepam or a similar drug.

The selection of anticonvulsant (anti-epileptic) drug depends on the type of epilepsy, the age of the patient, and his or her particular response to individual drug treatment.

Generalized epilepsy In this form of epilepsy, there is widespread disturbance of electrical activity in the brain, and loss of consciousness occurs at the outset. In its simplest form, a momentary loss of consciousness occurs during which the sufferer may stare into space. This is called an absence seizure, and mainly affects children. Seizures do not occur.

Another form of generalized epilepsy causes a brief jerk of a limb (myoclonus).

The most severe type is a tonic-clonic (grand mal) seizure, which is characterized by loss of consciousness and seizures that may last for a few minutes.

Sufferers may have one or more of these types of generalized epilepsy. Sodium valproate, lamotrigine, topiramate, levetiracetam, or the benzodiazepines are normally used for these types of epilepsy.

Partial (focal) epilepsy This type of epilepsy is caused by an electrical disturbance in only one part of the brain. The result is a disturbance of function, such as an abnormal sensation or movement of a limb, without loss of consciousness. Known as a simple partial seizure, this may precede a more serious attack associated with loss of consciousness (complex partial seizure), which may in turn progress to a generalized convulsive seizure.

Carbamazepine, lamotrigine, or phenytoin may be prescribed for this type of epilepsy.

Status epilepticus Repeated attacks without full recovery between, or a single attack lasting more than 10 minutes, occur in this form of epilepsy. Emergency treatment is required.

HOW THEY WORK

Brain cells bring about body movement by electrical activity that passes through the nerves to the muscles. In an epileptic seizure, uncontrolled electrical activity starts in one part of the brain and spreads to other parts, causing uncontrolled stimulation of brain cells. Most of the anticonvulsants have an inhibitory effect on brain cells and damp down electrical activity, preventing the excessive build-up that causes epileptic seizures.

HOW THEY AFFECT YOU

Ideally, the only effect an anticonvulsant should have is to reduce or prevent epileptic seizures. Unfortunately, no drug prevents seizures without potentially affecting normal brain function, often leading to poor memory, inability to concentrate, lack of coordination, and lethargy. It is important, therefore, to find a drug and dosage sufficient to prevent seizures without causing unacceptable side effects. The dose has to be carefully tailored to the individual. It is usual to start with a low dose of a selected drug and to increase it gradually until a balance is achieved between control of seizures and the occurrence of side effects, many of which wear off after the first weeks of treatment.

Blood tests are used to monitor levels of some anticonvulsants in the body as an aid to dose adjustment.

RISKS AND SPECIAL PRECAUTIONS

Each anticonvulsant has its own specific adverse effects and risks; and some affect the liver’s ability to break down other drugs and may influence the action of other drugs you are taking. Doctors try to prescribe the minimum number of anticonvulsants needed to control the seizures to reduce the risk of such interactions occurring.

Some anticonvulsants pose risks to a developing baby; if you are hoping to become pregnant, you should discuss the risks, and whether your medication should be changed, with your doctor. People taking anticonvulsants need to take them regularly as prescribed. If levels of anticonvulsant in the body fall suddenly, seizures are very likely to occur. The dose should not be reduced or treatment stopped, except on a doctor’s advice. Certain driving restrictions may apply if you have had a seizure; you need to report this to the Driver and Vehicle Licensing Agency (DVLA).

If, for any reason, anticonvulsant drug treatment needs to be stopped, the dose should be reduced gradually. People on anticonvulsant therapy are advised to carry an identification tag giving full details of their condition and treatment.

COMMON DRUGS

Carbamazepine, Clobazam, Clonazepam, Diazepam, Ethosuximide, Gabapentin, Lamotrigine, Levetiracetam, Lorazepam, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Sodium valproate, Tiagabine, Topiramate, Vigabatrin

Drugs for parkinsonism

Parkinsonism is a general term used to describe shaking of the head and limbs, muscular stiffness, an expressionless face, and inability to control or initiate movement. It is caused by an imbalance of chemicals in the brain; the effect of acetylcholine is increased by a reduction in the action of dopamine.

The most common cause of parkinsonism is Parkinson’s disease, degeneration of the dopamine-producing cells in the brain. Other causes include the side effects of certain drugs, notably antipsychotics, and narrowing of the blood vessels in the brain.

WHY THEY ARE USED

Drugs can relieve the symptoms of parkinsonism but, unfortunately, the degeneration of brain cells in Parkinson’s disease cannot be halted, although drugs can minimize symptoms for many years.

HOW THEY WORK

Drugs to treat parkinsonism restore the balance between the chemicals dopamine and acetylcholine. They fall into two main groups: those that reduce the effect of acetylcholine (anticholinergic drugs) and those that boost the effect of dopamine.

Anticholinergics combine with receptors on brain cells, preventing acetylcholine from binding to them. This action reduces acetylcholine’s relative overactivity and restores the balance with dopamine.

Dopamine cannot pass from the blood to the brain, and therefore cannot be given to boost its levels in the brain. Instead, levodopa (L-dopa), the chemical from which it is naturaly produced in the brain, is combined with carbidopa (as co-careldopa) or benserazide (as co-beneldopa) to prevent it from being converted to dopamine before it reaches the brain. Amantadine (also used as an antiviral) boosts dopamine levels in the brain by stimulating its release. Dopamine’s action can also be boosted by other drugs, including bromocriptine, pergolide, or apomorphine ATTN (injection only), which mimic the action of dopamine.

CHOICE OF DRUG

Anticholinergics are used to treat parkinsonism due to antipsychotic drugs, which have dopamine-blocking properties. They are not generally used to treat parkinsonism of unknown cause because they are less effective and may increase cognitive impairment. L-dopa is usually given when the disease impairs walking; its effectiveness usually wanes after two to five years, in which case other dopamine-boosting drugs may also be prescribed.

COMMON DRUGS

Dopamine-boosting drugs Amantadine, Apomorphine, Bromocriptine, Cabergoline, Entacapone, Levodopa (as co-beneldopa/co-careldopa), Pergolide, Pramipexole, Ropinirole, Selegiline

Anticholinergic drugs Orphenadrine, Procyclidine, Trihexyphenidyl/benzhexol

Drugs for dementia

Dementia is a decline in mental function severe enough to affect normal social or occupational activities. It can be sudden and irreversible, due to a stroke or head injury for example. It can also develop gradually and may be a feature of disorders such as poor circulation in the brain, multiple sclerosis, and Alzheimer’s disease. Much research is in progress on the cause of Alzheimer’s disease, the single most common cause of dementia.

WHY THEY ARE USED

Drugs called acetylcholinesterase inhibitors have been found to improve the symptoms of dementia in Alzheimer’s disease, although they do not prevent its long-term progression.

HOW THEY WORK

In healthy people, acetylcholinesterase (an enzyme in the brain) breaks down the neurotransmitter acetylcholine, balancing its levels and limiting its effects. In Alzheimer’s disease, there is a deficiency of acetylcholine. Acetylcholinesterase inhibitors block the action of the enzyme acetylcholinesterase, raising brain levels of acetylcholine, thus increasing alertness and slowing the rate of deterioration.

HOW THEY AFFECT YOU

Following assessment by a specialist of mental function, drug treatment is started at a low dose and increased gradually to minimize side effects. Any improvements should begin to appear in about three weeks. Assessment is repeated at six-monthly intervals to decide if the treatment is beneficial.

RISKS AND SPECIAL PRECAUTIONS

It is important to continue taking these drugs if they prove effective because there is a gradual loss of improvement after treatment is stopped. Side effects include urinary difficulties, nausea, vomiting, and diarrhoea. These drugs may increase the risk of seizures in some people.

COMMON DRUGS

Acetylcholinesterase inhibitors Donepezil, Galantamine, Memantine, Rivastigmine

Nervous system stimulants

A person’s state of mental alertness varies throughout the day and is under the control of chemicals in the brain, some of which are depressant, causing drowsiness, and others that are stimulant, heightening awareness.

It is thought that an increase in the activity of the depressant chemicals may be responsible for a condition called narcolepsy, which is a tendency to fall asleep during the day for no obvious reason. In this case, the nervous system stimulants are administered to increase wakefulness. These drugs include the amphetamines (usually dexamfetamine), the related drug methylphenidate, and modafinil. Amphetamines are used less often these days because of the risk of dependence. A common home remedy for increasing alertness is caffeine, a mild stimulant that is present in coffee, tea, and cola. Respiratory stimulants related to caffeine are used to improve breathing.

WHY THEY ARE USED

In adults who suffer from narcolepsy, some of these drugs prevent excessive drowsiness during the day. Stimulants do not cure narcolepsy and, since the disorder usually lasts throughout the sufferer’s lifetime, may have to be taken indefinitely. Methylphenidate or dexamfetamine are sometimes given to children suffering from attention deficit hyperactivity disorder (ADHD). Stimulants were once used as part of the treatment for obesity because reduced appetite is a side effect of amphetamines but they are no longer thought appropriate for weight reduction. Diet is now the main treatment, together with orlistat if necessary.

Caffeine is added to some analgesics to counteract the effects of caffeine withdrawal, which can cause headaches, but no clear medical justification exists for this.

Respiratory stimulants, such as theophylline, aminophylline, and doxapram, are used to improve breathing. They act on the respiratory centre, the part of the brain that controls breathing. They are sometimes used in hospitals to help people who have difficulty in breathing, mainly very young babies and adults with severe chest infections.

Apart from their use in narcolepsy, nervous system stimulants are not useful in the long term because the brain soon develops tolerance to them.

HOW THEY WORK

The level of wakefulness is controlled by a part of the brain stem called the reticular activating system (RAS). Activity in this area depends on the balance between chemicals, some of which are excitatory (including norepinephrine (noradrenaline)), and some inhibitory, such as gamma aminobutyric acid (GABA). Stimulants promote release of noradrenaline, increasing activity in the RAS and other parts of the brain, so raising alertness.

HOW THEY AFFECT YOU

In adults, the central nervous system stimulants taken in the prescribed dose for narcolepsy increase wakefulness, thereby allowing normal concentration and thought processes to occur. They may also reduce appetite and cause tremors. In hyperactive children, they reduce the general level of activity to a more normal level and increase the attention span.

RISKS AND SPECIAL PRECAUTIONS

Some people, especially the elderly or those with previous psychiatric problems, are particularly sensitive to stimulants and may experience adverse effects, even when the drugs are given in comparatively low doses. They need to be used with caution in children because they can retard growth if taken for prolonged periods. An excess of these drugs given to a child may depress the nervous system, producing drowsiness or even loss of consciousness. Palpitations may also occur.

These drugs reduce the level of natural stimulants in the brain, so after regular use for a few weeks a person may become physically dependent on them for normal function. If they are abruptly withdrawn, the excess of natural inhibitory chemicals in the brain depresses central nervous system activity, producing withdrawal symptoms. These may include lethargy, depression, increased appetite, and difficulty in staying awake.

Stimulants can produce overactivity in the brain if used inappropriately or in excess, resulting in extreme restlessness, sleeplessness, nervousness, or anxiety. They also stimulate the sympathetic branch of the autonomic nervous system, causing shaking, sweating, and palpitations. More serious risks of exceeding the prescribed dose are seizures and a major disturbance in mental functioning that may result in delusions and hallucinations. Because these drugs have been abused, amphetamines and methylphenidate are classified as controlled drugs.

COMMON DRUGS

Respiratory stimulants Doxapram, Theophylline/aminophylline

Other drugs Atomoxetine, Caffeine, Dexamfetamine, Methylphenidate, Modafinil

Drugs for migraine

Migraine is a term applied to recurrent severe headaches affecting only one side of the head and caused by changes in the blood vessels around the brain and scalp. They may be accompanied by nausea and vomiting and preceded by warning signs, usually an impression of flashing lights or numbness and tingling in the arms. Occasionally, speech may be impaired, or the attack may be disabling. The underlying cause of migraine is uncertain, but an attack may be triggered by a blow to the head, physical exertion, certain foods and drugs, or emotional factors such as excitement, tension, or shock. A family history of migraine also increases the chance of an individual suffering from it.

WHY THEY ARE USED

Drugs are used either to relieve symptoms or to prevent attacks. Different drugs are used in each approach, but none cures the underlying disorder. However, a susceptibility to migraine headaches can clear up spontaneously and, if you are taking drugs regularly, your doctor may recommend that you stop them after a few months to see if this has happened.

In most people, migraine headaches can be relieved by a mild analgesic (painkiller), such as paracetamol or a non-steroidal anti-inflammatory drug (NSAID), or a stronger one like codeine (see Analgesics). If nausea and vomiting accompany the migraine, tablets may not be absorbed sufficiently from the gut. Absorption can be increased if they are taken as soluble tablets in water or with an anti-emetic.

Some drugs used to relieve attacks can be given by injection, inhaler, nasal spray, or suppository. Preparations that contain caffeine should be avoided since headaches may be caused by excessive use or on stopping treatment. 5HT1 agonist drugs (such as sumatriptan) are used if analgesics are not effective. Ergotamine is used less often now.

The factors that trigger an individual’s attacks should be identified and avoided. Anti-anxiety drugs are not usually prescribed if stress is a precipitating factor because of the potential for dependence. If the attacks occur more often than once a month and significantly disrupt daily life, drugs to prevent migraine may be taken every day. Drugs used to prevent migraine are beta blockers, such as metoprolol or propranolol, and pizotifen (an antihistamine and serotonin blocker). Other drugs that have been used include amitriptyline (an antidepressant), verapamil, and cyproheptadine.

HOW THEY WORK

The symptoms of a migraine attack begin when blood vessels surrounding the brain constrict, producing the typical migraine warning signs. The constriction is thought to be due to certain chemicals found in food or produced by the body. The neurotransmitter serotonin causes large blood vessels in the brain to constrict. Pizotifen and propranolol block the effect of chemicals on blood vessels, thereby preventing attacks.

The next stage of a migraine attack occurs when blood vessels in the scalp and around the eyes dilate (widen). As a result, chemicals called prostaglandins are released, producing pain. Aspirin and paracetamol relieve this pain by blocking prostaglandins. Codeine acts directly on the brain, altering pain perception (see Analgesics). Ergotamine and 5HT1 agonists relieve pain by narrowing dilated blood vessels in the scalp.

HOW THEY AFFECT YOU

Each drug has its own adverse effects. 5HT1 agonists may cause chest tightness and drowsiness. Ergotamine may cause drowsiness, tingling sensations in the skin, cramps, and weakness in the legs, and vomiting may be made worse. Pizotifen may cause drowsiness and weight gain. See propranolol and analgesics for the effects of these drugs.

RISKS AND SPECIAL PRECAUTIONS

5HT1 agonists should not usually be used by people with high blood pressure, angina, or coronary heart disease. Ergotamine can damage blood vessels by prolonged overconstriction, so it should be used with caution by those with poor circulation. Excessive use can lead to dependence and many adverse effects, including headache. You should not take more than your doctor advises in any one week.

HOW THEY ARE ADMINISTERED

These drugs are usually taken by mouth as tablets or capsules. Sumatriptan can also be taken as an injection or a nasal spray. Ergotamine can be taken as suppositories, or as tablets that dissolve under the tongue.

COMMON DRUGS

Drugs to prevent migraine Amitriptyline, Cyproheptadine, Pizotifen, Propranolol, Sodium valproate, Verapamil

5HT1 agonists Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan

Other drugs to relieve migraine Codeine, Ergotamine, NSAIDs, Paracetamol, Tolfenamic acid

Anti-emetics

Drugs used to treat or prevent vomiting or the feeling of sickness (nausea) are known as anti-emetics. Vomiting is a reflex action for getting rid of harmful substances, but it may also be a symptom of disease. Vomiting and nausea are often caused by a digestive tract infection, travel sickness, pregnancy, or vertigo (a balance disorder involving the inner ear). They can also occur as a side effect of some drugs, especially those used for cancer, radiation therapy, or general anaesthesia.

Commonly used anti-emetics include metoclopramide, domperidone, haloperidol, cyclizine, ondansetron, granisetron, prochlorperazine, promethazine, and cinnarizine. The phenothiazine and butyrophenone drug groups are also used as antihistamines and to treat some types of mental illness (see Antipsychotic drugs).

WHY THEY ARE USED

Doctors usually diagnose the cause of vomiting before prescribing an anti-emetic because the vomiting may be caused by an infection of the digestive tract or some other condition of the abdomen that might require treatment such as surgery. Treating only the vomiting and nausea might delay diagnosis, correct treatment, and recovery.

Anti-emetics may be taken to prevent travel sickness (using one of the antihistamines) or vomiting resulting from anticancer and other drug treatments (metoclopramide, haloperidol, domperidone, ondansetron, and prochlorperazine, for example).

Vertigo is a spinning sensation in the head often accompanied by nausea and vomiting. It is usually caused by a disease affecting the organ of balance in the inner ear. Anti-emetics are prescribed to relieve the symptoms.

Ménière’s disease is a disorder in which excess fluid builds up in the inner ear, causing vertigo, noises in the ear, and gradual deafness. It is usually treated with cinnarizine, betahistine, prochlorperazine, or an anti-anxiety drug. A diuretic may also be given to reduce the excess fluid in the ear.

Anti-emetics are also occasionally used to relieve cases of severe vomiting during pregnancy. You should not take an anti-emetic during pregnancy except on medical advice. No anti-emetic drug should be taken for longer than a couple of days without consulting your doctor.

HOW THEY WORK

Nausea and vomiting occur when the vomiting centre in the brain is stimulated by signals from three places in the body: the digestive tract, the part of the inner ear controlling balance, and the brain itself via thoughts and emotions and via its chemoreceptor trigger zone, which responds to harmful substances in the blood. Anti-emetic drugs may act at one or more of these places. Some help the stomach to empty its contents into the intestine. A combination may be used that works at different sites and has an additive effect.

HOW THEY AFFECT YOU

As well as treating vomiting and nausea, many anti-emetic drugs may make you feel drowsy. However, for preventing travel sickness on long journeys, a sedating antihistamine may be an advantage.

Some anti-emetics (in particular, phenothiazines and antihistamines) can block the parasympathetic nervous system (see Autonomic nervous system), causing dry mouth, blurred vision, or difficulty in passing urine. Phenothiazines may also lower blood pressure, leading to dizziness or fainting.

RISKS AND SPECIAL PRECAUTIONS

Because some antihistamines can make you drowsy, it may be advwisable not to drive while taking them. Phenothiazines, butyrophenones, and metoclopramide can produce uncontrolled movements of the face and tongue, so they are used with caution in people with parkinsonism.

COMMON DRUGS

Antihistamines Cinnarizine, Cyclizine, Meclozine, Promethazine

Phenothiazines Chlorpromazine, Levomepromazine, Perphenazine, Prochlorperazine, Trifluoperazine

5HT3 antagonists Granisetron, Ondansetron, Tropisetron

Butyrophenones Haloperidol

Other drugs Aprepitant, Betahistine, Dexamethasone, Domperidone, Hyoscine hydrobromide, Metoclopramide, Nabilone


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